Associations Between Aldosterone Antagonist Therapy and Risks of Mortality and Readmission Among Patients With Heart Failure and Reduced Ejection Fraction

Study Questions:

What is the safety and efficacy of aldosterone antagonists (aldo-I) in clinical practice in patients with systolic heart failure (HF)?

Methods:

This was an analysis of the Get With The Guidelines-Heart Failure database. Patients analyzed had to have had a recent HF admission, a left ventricular ejection fraction (LVEF) ≤35%, and a serum creatinine <2.5 mg/dl in men and <2.0 mg/dl in women. The treatment group was comprised of those who received aldo-I, and the controls were all other aldo-I eligible patients who did not receive aldo-I therapy at hospital discharge. The outcome measures of interest included all-cause mortality, cardiovascular readmission, and HF readmission at 3 years and hyperkalemia readmission at 30 days and 1 year.

Results:

There were 5,887 HF patients eligible for aldo-I therapy, 1,070 (18%) of whom were in the treatment group. Patients who received aldo-I tended to be younger, with better renal function, lower LVEFs, and high frequency of angiotensin-converting enzyme inhibitor and diuretic use. All-cause mortality rates were similar in those treated with aldo-I (49.9%) versus controls (51.2%; p = 0.62; adjusted hazard ratio [HR], 1.04 [0.96-1.1]). The cumulative incidence of HF readmission over 3 years was significantly lower in the aldo-I treatment group (39% vs. 45%; p < 0.001; adjusted HR, 0.87 [0.77-0.98]). Rates of hyperkalemia associated with readmission were higher in aldo-I patients (9% vs. 6% at 30 days; HR, 1.5 [1.2-1.8]).

Conclusions:

Patients treated with aldo-I upon hospital discharge for HF had lower readmission rates for HF. However, there were no differences in overall survival, and higher rates of readmission for hyperkalemia.

Perspective:

This was a more ‘true to life’ examination of aldosterone antagonist therapy in patients with systolic HF. The gains in mortality noted in randomized controlled trials were not noted in this study. However, reductions in HF readmissions—a clinically relevant outcome—were lower. A major limitation of this analysis that needs considered is that drug therapy was not randomized. While all patients were deemed aldo-I eligible, there were differences at baseline in EF, renal function, etc., between controls and the aldo-I group. Only 18% of eligible patients received aldo-I therapy. While statistics can attempt to control for these differences, it is not a pure ‘apples to apples’ comparison. Practitioners should consider aldo-I therapy in patients with low EFs, but also need to closely monitor potassium levels.